We propose to examine the use of a monovalent antigen fragment (antigen D) isolated from timothy pollen extracts to treat patients initiating treatment for April 1 to May 1 which is just before the onset of the pollen season. Such coseasonal therapy with standard allergen extracts is not possible as the amount of allergen safely administered would be insufficient and the risk of systemic reactions high. On the other hand, the very weak allergenicity of antigen D permits the use of relatively large amounts of material over a short duration (10 to 13 weeks). Patients receiving coseasonal therapy with antigen D will be compared with either control patients (not treated for their timothy allergy) or patients treated with the whole timothy extract. Clinical effectiveness of a given mode of treatment will be based upon daily diaries (symptom scores) and leukocyte histamine release responses of the patients. Recent experiments demonstrated that antigen D can be covalently linked to various proteins (human serum, albumin or IgG) that persist in the circulation for prolonged periods of time. Experiments are now in progress to determine if antigen D linked to the above proteins may provide not only improved clinical protection but also reduce the frequency of injections.